dr. ehsan ahmadpour (orcid id : 0000-0003-1202-6147) …...strongyloides stercoralis, and affects...

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leDR. EHSAN AHMADPOUR (Orcid ID : 0000-0003-1202-6147)

Article type : Review

Strongyloides stercoralis Infection in Human Immunodeficiency Virus

(HIV)-Infected Patients and Related Risk Factors: a Systematic Review

and Meta-analysis

Ehsan Ahmadpour1,2,*, Mohammad Ali Ghanizadegan3, Atefeh Razavi3, Mahsa Kangari3, Rouhollah Seyfi3, Maryam Shahdust3, Ali Yazdanian3, Hanie Safarpour3, Hossein Bannazadeh Baghi2,1, Mehdi Zarean4, Seyed Abdollah Hosseini5, Roghayeh Norouzi6, Mina Ebrahimi7, Berit Bangoura8

1Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 2Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 3Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran 4Department of Parasitology and Mycology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 5Toxoplasmosis Research Center, Mazandaran University of Medical Sciences, Sari, Iran 6Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran 7Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 8Department of Veterinary Sciences, College of Agriculture and Natural Resources, University of Wyoming, Laramie, Wyoming, USA

*Corresponding authors: Ehsan Ahmadpour, Ph.D

Email: [email protected], [email protected]

Address: Department of Parasitology and Mycology, Tabriz university of Medical Sciences,

Tabriz, Iran

Tel: +98 413 5428595, Fax: +98 413 337 3745

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/tbed.13310This article is protected by copyright. All rights reserved.

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Abstract

Strongyloidiasis is caused by nematode infections of the genus Strongyloides, mainly

Strongyloides stercoralis, and affects tens of millions of people around the world. S.

stercoralis hyperinfection and disseminated strongyloidiasis are unusual but potentially fatal

conditions mostly due to Gram-negative bacteremia and sepsis, primarily affecting

immunocompromised patients. Infections with immunosuppressive viruses such as human

immunodeficiency virus (HIV) and Human T-cell leukemia virus type 1 (HTLV-1) have been

reported as risk factors for strongyloidiasis. Hyperinfection syndrome has been described in

HIV-positive patients following the use of corticosteroids or during immune reconstitution

inflammatory syndrome (IRIS). In this research, we conducted a global systematic review

and meta-analysis to assess the seroprevalence and odds ratios (ORs) of S. stercoralis

infections in HIV infected patients. A total of 3,649 records were screened, 164 studies were

selected and evaluated in more detail, and 94 studies were included in the meta-analysis. The

overall pooled prevalence of S. stercoralis infection in HIV positive patients was 5.1 %

(CI95%: 4 % - 6.3 %), and a meta-analysis on six studies showed that with a pooled OR of

1.79 (CI95%: 1.18 - 2.69 %) HIV positive men are at a higher risk of S. stercoralis infections

(P<0.0052) compared to HIV positive women.

Keywords: Strongyloidiasis, Human immunodeficiency virus, prevalence, systematic review

This article is protected by copyright. All rights reserved.

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Introduction

Nematoda, or roundworms, represent an important phylum of human and animal parasites.

Within the roundworms, the genus Strongyloides comprises several soil transmitted parasitic

species, some of which are zoonotic like Strongyloides (S.) stercoralis and S. fuelleborni

(Keiser & Nutman, 2004; Thanchomnang et al., 2017). Of those, S. stercoralis is of

worldwide importance, being endemic to tropical, subtropical, and temperate areas (Garcia,

1999; Segarra-Newnham, 2007). Interestingly, this nematode features two different life-cycle

forms, a free-living and a parasitic cycle. S. stercoralis infections in animals and humans

occur predominantly percutaneously by filariform larvae though an infection can also result

from oral uptake (Thamsborg, Ketzis, Horii, & Matthews, 2017). After penetrating the skin,

major proportion of the larvae enter vessels and are carried to the lungs. The larvae then

migrate through the lung tissue, are coughed up and swallowed with sputum, and finally

reach the small intestine. Other larvae can travel directly to the small intestine (Thamsborg et

al., 2017). Larvae mature into adult females in the intestinal mucosa, especially the

duodenum and upper jejunum. Females produce eggs by parthenogenesis, and mostly

rhabditiform larvae hatch already before eggs are passed into the environment. These hatched

larvae can either cause autoinfection or be passed in stool to initiate a free-living cycle (Olsen

et al., 2009). This worm infects more than 100 million people worldwide annually

(Puthiyakunnon et al., 2014). Autoinfection is repeated generations that appears when the

non-infective larvae become infective filariform larvae in the same host. The filariform larvae

could enter the intestinal wall or the perianal skin and will cause a persistent infection (Keiser

& Nutman, 2004).

Clinical signs and symptoms in infected humans vary greatly. More than 50 % of infected

patients are asymptomatic, while up to 2.5% of infected patients show a so-called

hyperinfection as result from autoinfection, i.e. reinfection with larvae produced by female


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worms present in the own intestine and subsequent systemic dissemination of disease (Lam,

Tong, Chan, & Siu, 2006; Segarra-Newnham, 2007). Hyperinfection occurs mostly in

patients with an impaired cell mediated immune system (Grove, 1996; Huis, Sun, Hung, &

Colebunders, 2012; Keiser & Nutman, 2004). Human immunodeficiency virus (HIV)

infection, Human T-cell leukemia virus type 1 (HTLV-1) infection, alcoholism, low

socioeconomic status, white race, male gender, corticosteroid therapy, hematologic

malignancy, and malnutrition have been reported as risk factors for strongyloidiasis

(Davidson, Fletcher, & Chapman, 1984; Jongwutiwes, Waywa, Silpasakorn,

Wanachiwanawin, & Suputtamongkol, 2014; Keiser & Nutman, 2004; Schär et al., 2013;

Walzer et al., 1982)

HIV infection is mainly sexually transmitted, however, people may also be infected by

contact with HIV-positive blood or vertically during pregnancy, childbirth and breast-feeding

(John-Stewart, 2018; UNICEF., HIV/AIDS., & Organization, 2002). The number of people

infected with HIV is estimated to be about 36.9 million (31.1 million–43.9 million)

worldwide (in 2017). Due to its detrimental effect on the human immune system, especially

depletion of CD4+ lymphocytes (Stricker et al., 1987; Veenhuis, Clements, & Gama, 2019),

HIV increases the probability of severe outcome in secondary infections by bacteria

(Pawlowski, Jansson, Sköld, Rottenberg, & Källenius, 2012), fungi (Moreira et al., 2016),

viruses - - -Samaniego, & Soriano, 2001), and also

parasites (Ahmadpour et al., 2014; Luft & Remington, 1992). Several studies have shown a

relation between HIV infection, S. stercoralis infection and hyperinfection (Hagelskjaer,

1994; Siegel & Simon, 2012). This systematic review and meta-analysis was designed to

comprehensively determine pooled seroprevalence of S. stercoralis in relation to confounding

factors for increased seropositivity in HIV positive population.


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Methods

Search strategy

The meta-analysis was performed in accordance with the Preferred Reporting Items for

Systematic Reviews and Meta-Analysis (PRISMA) statement (Moher, Liberati, Tetzlaff, &

Altman, 2009). Four databases, namely PubMed, Science Direct, Scopus, and Google scholar

were searched for articles solely in English that were published between January 2000 and

August 2017. Keywords f h w “ t n y i i i ” “Strongyloides

stercoralis” “S. stercoralis” “H n I n fi i n y Vi ” n “ HIV”.

Study selection

All descriptive, cross-sectional, case–control and epidemiology studies reporting on overall

prevalence rates for S. stercoralis infections in HIV infected populations were included.

Exclusion criteria included: articles that used diagnostic methods for detection of S.

stercoralis infection other than serological, microscopic, molecular test (PCR), culture,

and/or direct detection methods; articles written in a language other than English; non-peer

reviewed or popular scientific publications, abstracts, national conference proceedings; and

duplicate studies with overlapping data, studies with non-random sampling methods and

those studying specific limited populations (pregnant women, transplantation and cancer

patients). The suitability of all studies according to the defined criteria was judged

independently by three different authors. Any differences in judgment were resolved by

discussion among the authors. After selecting articles, the authors recorded relevant

information in a standard data extraction form. A flow diagram of the study selection process

is shown in Fig. 1.


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Data extraction

Precisely extracted information from the included studies (n = 94) was collected in a table.

Information collected referred to year of publication, first author, country and region of study,

study location, total sample size, number of male and female participants, number of subjects

with positive test results, age distribution, S. stercoralis diagnostic methods, CD4 count, and

cases of diarrhea.

Statistical analysis

The meta-analysis was performed using Comprehensive Meta-Analysis 2.2 software (Biostat

Inc., Englewood, NJ, USA). The pooled overall prevalence of S. stercoralis and its 95%

confidence interval was calculated using a random-effects model. In the subgroup analysis

the pooled prevalence of S. stercoralis, in different countries and regions and using different

diagnostic methods, was calculated. The forest plot, for the subgroup analysis of diagnostic

methods, was reported. Additionally, separate meta-analyses were performed on the eligible

studies to evaluate the effect of diarrhea, low CD4 count (< 200 /μ L) nd patient sex on

the risk of infection with S. stercoralis. Heterogeneity in all meta-analyses was assessed

using I2 in x n C h n’ Q t t. b i ti n bi w in E ’ int pt

and visual inspection of the funnel plot. The level of significance for all tests was p < 0.05.

Results

Study selection

The search in PubMed, Science Direct, Scopus, and Google scholar databases revealed 5,550

records. After removing duplicates, 3,649 records were screened using their titles and/or

abstracts. One-hundred sixty-four studies were selected to be evaluated in more detail using

their full-texts, and 94 studies were finally included in the meta-analysis (Fig. 1).


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Overall Prevalence

Collectively, a total of 26,473 individuals from 34 countries worldwide were included in the

meta-analysis (Table 1). The overall pooled prevalence of S. stercoralis infection in HIV-

positive (HIV+) patients was reported as 5.1 % (CI95%: 4 % - 6.3 %). Substantial

heterogeneity was observed between the included studies (I2: 95.1 %, p < 0.05). The

estimated pooled prevalence varied significantly using different diagnostic methods for

detection of S. stercoralis infection (p < 0.05). Most of the studies used microscopy to

diagnose the infection and detected a pooled prevalence of 3.6 % (CI95%: 2.6 % - 4.7 %)

(Fig. 2). The pooled estimate using culture (Fig. 3), serologic methods (Fig. 4) and PCR was

10.8 % (CI95%: 7.1 % - 15.1 %), 12.4 % (CI95%: 6.9 % - 19.3 %) and 3.9 % (CI95%: 2.1 %

- 6.1 %), respectively (Table 2). High heterogeneity was also observed in the subgroup meta-

analyses of diagnostic methods, except for PCR, which was only used by two studies. The

statistically significant E ’ i n p < 0.05) and the shape of funnel plot indicate that

there is a high probability of publication bias (Fig. 5).

Confounding Factors

The male to female ratio of participants was 45.5 % to 54.5 % and the average age was 34.2 ±

9.7 years. A meta-analysis on six studies showed that with a pooled OR of 1.79 (CI95%: 1.18

- 2.69) HIV+ men are at a higher risk of S. stercoralis infections (P<0.0052) compared to

HIV+ women (Table 3).

In a meta-analysis we performed on a subset of 14 eligible studies providing data on diarrhea

occurrence, participants with diarrhea had a pooled OR of 1.79 % (CI95%: 1.18 % - 2.69 %)

for the infection with S. stercoralis compared to participants without diarrhea (P<0.0005).

Moreover, a meta-analysis performed on eight eligible studies showed a pooled OR of 4.56


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(CI95%: 2.44 - 8.49) for acquiring an infection with S. stercoralis in patients with CD4+ cell

nt f t h n 200 /μ P<0.0001).

Geographic Distribution

The geographic distribution of studies significantly affected the pooled estimate (Fig. 6).

Regarding individual countries, the pooled estimate was highest in the US (25.5 %, CI95%:

20.3 % - 31.6 %) and lowest in Nepal (0.3 %, CI95%: 0.1 % - 1.1 %). Ethiopia was the

country with the highest number of studies with a pooled prevalence of 5.6% (CI95%: 3.7%-

8.3%). Moreover, the countries were grouped according to the WHO Global Burden of

Diseases regions and the pooled estimate significantly varied between the regions. Looking at

broader geographic regions, most of the studies were performed in the African Region with a

pooled prevalence of 4.2 % (CI95%: 3 % - 5.6 %). The highest prevalence was in the

Western Pacific region with 11.5 % (CI95%: 5.7 % - 22.0 %) and the lowest was in the

Eastern Mediterranean Region with 0.5 % (CI95%: 0.1 % - 1.8 %). The pooled estimate in

Region of the Americas, European Region and Asia Region were 11.3 % (CI95%: 5.7 % -

18.4 %), 8.6 % (CI95%: 3.5 % - 15.5 %) and 3.3 % (2.1 % - 4.9 %), respectively (Table 2).

Discussion

This study was designed to evaluate occurrence and risk factor for strongyloidiasis, a

neglected tropical disease which occurs worldwide, in HIV+ patients as a highly vulnerable

group. By reviewing published original articles on strongyloidiasis in HIV+ patients, we

assessed prevalence of S. stercoralis, geographic distribution, and additional risk factors for

this major risk population.


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Our analysis revealed a significant proportion of S. stercoralis positive cases within HIV+

patients (5.1 %). Immunocompromised people are the most at risk population for developing

fatal illnesses including strongyloidiasis (Henriquez-Camacho et al., 2016). Despite variable

strength of association, HIV infected individuals are more likely to acquire S. stercoralis

infections (Schär et al., 2013). Considering the differences in immunosuppression by drugs

such as corticosteroids and HIV, it was argued before that HIV patients may have a sustained

ability to control S. stercoralis infections making HIV less predisposing to this parasitosis

than other immunosuppressive conditions (Siegel & Simon, 2012). Accordingly, the most

severe clinical cases (hyperinfection syndrome) are seen rather in people with conditions like

the HLTV-1 infection than in HIV+ patients (Marcos, Terashima, DuPont, & Gotuzzo, 2008).

The results obtained from this systematic review showed that the prevalence rate of S.

stercoralis in HIV+ patients using serological method (12.4%) was higher than other methods

(3.6% microscopy, 10.8% culture and 3.9% molecular assays). According to our litterateur

review, the prevalence obtained though in general serological assays for detection of

pathogens can yield a low sensitivity in HIV+ individuals due to the potentially reduced

humoral immune response (Lindoso, Moreira, Cunha, & Queiroz, 2018; Segarra-Newnham,

2007). This is not attributed to certain diagnostic tests being preferred for studies in different

regions since all described tests have used widely in different regions (Table 2, Fig. 2-4).

Thus, serological testing, as a convenient method, is considered a suitable method for S.

stercoralis detection, along with direct detection methods (microscopy). Interestingly, the

serological methods for detecting S. stercoralis infection in HIV+ patients showed high rates

between the diagnostic methods deployed. This is in line with earlier findings of a generally

higher sensitivity of serological compared to microscopical assays (Gétaz et al., 2019) which

may lead to a comparatively high detection sensitivity of serology even in

immunocompromised individuals. Major complications arising from strongyloidiasis are a


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persistent infection following repeated autoinfection, systemic dissemination of larvae, and

accordingly the development of potentially fatal systemic disease. Though our study was not

designed to judge the prevalence differences between HIV+ and HIV- negative individuals, it

i t nn in t th inf ti n p v n ’ in HIV+ p ti nt f wi y within th n f

the (known) overall populations in the respective regions.

Over all analyzed studies in this review, 54% of participants in the study were female and

46% male which represents roughly even distribution with a minor underrepresentation of

male patients. However, male sex was identified as predisposing factor for the overall

prevalence, seemingly making male sex a risk factor for S. stercoralis infections among

HIV+ individuals (P= 0.0005). We assume sex to be a confounder since other factors and

conditions might be relevant that have been shown to represent risk factors for S. stercoralis

infections in regional populations (Gétaz et al., 2019) and may show a different distribution

over women compared to men (such as age, other health conditions, alcohol consumption,

etc.).

In this study, regarding clinical signs, the occurrence of diarrhea as a potential indicator of

S. stercoralis infection was analyzed. Accordingly, the likelihood of infection was

significantly higher among patients with diarrhea occurrence (P= 0.0052). Given that the

most important complications of S. stercoralis infections stem from larval dissemination,

leading to the hyperinfection syndrome.

Beside, HIV infection is progressively associated with decrease of CD4+ lymphocytes

(Bosinger & Utay, 2015). The results of this systematic review indicated that the lower CD4+

counts were correlated to a higher probability of S. stercoralis infection (P <0.0001),

underlining the importance of the immune system in eliminating the parasite without

prolonged auto-infections.


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General worldwide prevalence rates of S. stercoralis in humans have been assessed in

numerous studies. Estimated prevalence varies from three million to one hundred million

infected persons (Puthiyakunnon et al., 2014; Schär et al., 2013). However, more detailed

epidemiological data of national and local S. stercoralis infection rates and populations at risk

have increasing clinical value. To our knowledge, this is the first meta-analysis into report

prevalence rates on a country-by-country basis considering the sensitivity of the diagnostic

methods used. Regional differences may be linked to the general prevalence of the pathogen

in different areas. The results of the present systematic review show that there is a generally

higher human prevalence of S. stercoralis infection in America (11.3%) than in the rest of the

world (8.6% in Europe, 4.2% in Africa and 3.3% in Asia), however, these data are also

incomplete, and information on many countries is missing as of now (Schar et al., 2013;

Vermund, 2014). However, the comparatively low prevalence rates for S. stercoralis

infections in HIV+ patients in the Eastern Mediterranean region and the Southeast Asian

i n t t h th n y w p v n in th i n ’ p p ti n .

Looking at infection sources, circulation of S. stercoralis within the human population

occurs directly or via soil, while dogs seem host both S. stercoralis strains of zoonotic

potential and strains not transmissible to humans (Jaleta et al., 2017). Thus, prevalence in

animals may not be used directly to estimate the potential human prevalence. Besides the

obviously different infection pressure for humans in different areas of the world, the observed

publication bias in the analyzed studies (such as sample size, participant selection criteria,

study methodology, etc.) may contribute to our observations though we assume regional

differences to be present indeed (Schar et al., 2013).

Our review and analysis have several limitations. Looking at the available studies,

it becomes obvious that data on infection prevalence is scant for S. stercoralis. Many studies

are designed to detect other Soil Transmitted Helminthes (STHs), leading to use of direct


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diagnostic methods with a suboptimal sensitivity for S. stercoralis detection. Many studies

had to be excluded because of incomplete data and unspecific reports on helminth infections

though they may have included S. stercoralis. Thus, currently S. stercoralis prevalences are

probably underestimated, and the heterogeneous prevalence data reported may partially be

caused by flaws in methodology. Therefore, variations in study design and methodology

among the included studies are an important limitation of this analysis. Publication bias is an

important threat to the authority of systematic reviews. To decrease the risk of publication

bias, we did a comprehensive search across various databases. However, as for any

systematic review, we cannot dismiss the influence of publication bias.

We conclude that S. stercoralis is of great importance and available data on HIV+ patients

indicates a high prevalence. Thus, HIV+ patients globally should be checked routinely for

this neglected parasitic infection, since anthelmintic treatment is readily available for known

cases. Overall, future studies should be designed to specifically test for S. stercoralis in high

risk populations, such as HIV+ individuals, and should use highly sensitive diagnostic

methods, such as the Koga Agar plate culture or the Baermann technique or a serological

ELISA. Future studies should also include HIV- comparison groups to enable judgment of

HIV status as a risk factor, especially for severe outcomes (hyperinfection syndrome).

Acknowledgment

We appreciate the excellent help provided by Dr. Spotin.

Conflict of Interest

The authors declared that they have no competing interests.


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Ethical statement

Not applicable.

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Table 1 Baseline characteristics of the included studies

No. First Author Year of

publication

Country Number of

Samples

Number of

patients

% Pos Diagnostic Method

1 Prasad KN 2000 India 59 1 1.69 Microscopy

2 Dreyfuss ML 2001 Tanzania 822 12 1.45 Microscopy

3 Feitosa G 2001 Brazil 365 20 5.47 Culture

4 Gassama A 2001 Senegal 318 3 0.94 Microscopy

5 Lebbad M 2001 Guinea-Bissau 37 5 13.51 Microscopy

6 Waywa D 2001 Thailand 288 23 7.98 Culture

7 Wiwanitkit V 2001 Thailand 60 2 3.33 Microscopy

8 Dowling JJ 2002 Malawi 162 8 4.93 Culture

9 Joshi M 2002 India 94 5 5.31 Microscopy

10 Adjei A 2003 Ghana 21 1 4.76 Serology

11 Arenas-Pinto A 2003 Venezuela 304 32 10.52 Culture

12 Botero JH 2003 Colombia 36 2 5.55 Culture

13 Datta D 2003 England 525 1 0.19 Microscopy

14 Kassu A 2003 Ethiopia 23 5 21.7 Culture

15 Marchi Blatt J 2003 Brazil 211 21 9.95 Culture

16 Okodua M 2003 Nigeria 35 1 2.85 Microscopy

17 Brown M 2004 Uganda 547 68 12.43 Culture

18 Hailemariam G 2004 Ethiopia 78 4 5.12 Microscopy

19 Kaminsky RG 2004 Honduras 133 10 7.51 Culture

20 Viney ME 2004 Uganda 700 84 12 Culture

21 Zali MR 2004 Iran 206 2 0.97 Microscopy

22 Pinlaor S 2005 Thailand 78 14 17.94 Microscopy

23 Silva CV 2005 Brazil 100 12 12 Culture

24 Chhin S 2006 Cambodia 80 12 15 Culture

25 Garcia C 2006 Peru 217 15 6.91 NR

26 Hosseinipour MC 2007 Malawi 266 2 0.75 Microscopy

27 Meamar AR 2007 Iran 781 2 0.25 Microscopy

28 Vignesh R 2007 India 245 3 1.22 Microscopy

29 Bachur TP 2008 Brazil 582 156 26.8 Microscopy

30 Lillie PJ 2008 England 107 2 1.86 Microscopy

31 Mariam ZT 2008 Ethiopia 109 7 6.42 Microscopy

32 Assefa S 2009 Ethiopia 214 27 12.61 Microscopy

33 Kawai K 2009 Tanzania 971 13 1.33 Microscopy

34 Kurniawan A 2009 Indonesia 318 1 0.31 Microscopy

35 Lule JR 2009 Uganda 491 90 18.32 Microscopy


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36 Viriyavejakul P 2009 Thailand 64 2 3.12 Microscopy

37 Werneck-Silva AL 2009 Brazil 690 1 0.14 NR

38 Getaneh A 2010 Ethiopia 192 23 11.97 Microscopy

39 Telele NF 2010 Ethiopia 143 14 9.79 NR

40 Tian L.G. 2010 China 46 0 0 Culture

41 Walson JL 2010 Kenya 1541 4 0.25 Microscopy

42 Akinbo FO 2011 Nigeria 2000 23 1.15 Microscopy

43 Alemu A 2011 Ethiopia 188 3 1.59 Microscopy

44 Brites C 2011 Brazil 123 6 4.87 NR

45 Cardoso LV 2011 Brazil 500 1 0.2 Culture

46 Chordia P 2011 India 239 14 5.85 Microscopy

47 Hochberg NS 2011 US 128 33 25.78 Serology

48 Idindili B 2011 Tanzania 421 57 13.53 Microscopy

49 Mascarello M 2011 Italy 138 15 10.86 Serology

50 Ojurongbe O 2011 Nigeria 96 1 1.041 Microscopy

51 Sanyaolu A 2011 Nigeria 65 1 1.53 Microscopy

52 Abaver D.T. 2012 Nigeria 480 5 1.04 Microscopy

53 Boaitey Y.A. 2012 Ghana 500 2 0.4 Microscopy

54 Boaitey YA 2012 Ghana 500 2 0.4 Microscopy

55 Costiniuk CT 2012 Canada 96 10 10.41 Serology

56 Nabha L. 2012 US 103 26 25.24 Serology

57 Roka M. 2012 Guinea 260 23 8.84 Microscopy

58 Sivaram M 2012 England 263 3 1.14 Microscopy

59 Tabaseera N 2012 Tanzania 100 0 0 Microscopy

60 Arndt MB 2013 Kenya 153 5 3.26 PCR

61 Dash M 2013 India 115 3 2.6 Microscopy

62 Fekadu S. 2013 Ethiopia 343 56 16.32 Microscopy

63 Gupta K. 2013 India 100 1 1 Microscopy

64 Janagond AB 2013 India 100 2 2 Microscopy

65 Kulkarni S 2013 India 65 1 1.53 Microscopy

66 Llenas-García J 2013 Spain 237 13 5.48 Serology

67 Mehta K.D. 2013 India 100 3 3 Microscopy

68 Mulu A 2013 Ethiopia 220 3 1.36 Microscopy

69 Rivero-Rodríguez 2013 Venezuela 56 15 26.78 Microscopy

70 Roka M. 2013 Guinea 273 28 10.25 Microscopy

71 Sadlier CL 2013 Ireland 90 2 2.22 Serology

72 Salvador F 2013 Spain 190 35 18.42 Serology

73 Teklemariam Z 2013 Ethiopia 371 15 4.04 Microscopy


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NR: not reported

74 Tiwari BR 2013 Nepal 745 2 0.26 Microscopy

75 da Silva H. 2014 Brazil 15 7 46.66 Culture

76 Mahmud M.A 2014 Ethiopia 372 1 0.26 Microscopy

77 Nkoa T 2014 Cameroon 332 3 0.9 Microscopy

78 Paboriboune P 2014 Laos 137 28 20.43 Microscopy

79 Salvador F 2014 Spain 28 13 46.42 Culture

80 Taye B 2014 Ethiopia 316 13 4.11 Microscopy

81 Vouking M.Z 2014 Cameroon 207 7 3.38 Microscopy

82 Ahmed NH 2015 India 142 5 3.52 Microscopy

83 Angal L 2015 Malaysia 131 9 6.87 Microscopy

84 Mengist HM 2015 Ethiopia 180 9 5 Microscopy

85 Mulu A. 2015 Ethiopia 105 4 3.8 Microscopy

86 Plumelle Y 2015 France 445 55 12.35 Microscopy

87 Hailu AW 2016 Ethiopia 18 5 27.77 Culture

88 Nsagha DS 2016 Cameroon 300 2 0.66 Microscopy

89 Shah S 2016 India 45 1 2.22 Microscopy

90 Shimelis T 2016 Ethiopia 491 22 4.48 Microscopy

91 Gedle D 2017 Ethiopia 323 5 1.54 Microscopy

92 Morawski BM 2017 Uganda 202 8 3.96 PCR

93 Senbeta D 2017 Ethiopia 238 7 2.94 Microscopy

94 Swathirajan CR 2017 India 829 15 1.8 Microscopy


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Table 2. Pooled prevalence of S. stercoralis in HIV positive patients and subgroup analyses.

Group Number of

studies

Pooled Prevalence

(CI 95%)

Heterogeneity

P value I2 Cochran Q

Total 94 5.1% (4%-6.3%) < 0.001 95.1% 2179.6

Diagnostic Method

Microscopy 73 3.6% (2.6%-4.7%) < 0.001 95% 1442.9

Culture 17 10.8% (7.1%-15.1%) < 0.001 92.3% 207.3

Serology 8 12.4% (6.9%-19.3%) < 0.001 88.7% 61.8

Molecular 2 3.9% (2.1%-6.1%) 0.763 - 0.09

The continent

America 17 11.3% (5.7%-18.4%) <0.0001 97.6 668.8

Europe 10 8.6% (3.5%-15.5%) <0.0001 95.9 221.8

Asia 29 3.3% (2.1%-4.9%) <0.0001 88.5 242.4

Africa 52 4.2% (3%- 5.6%) <0.0001 94.8 982.5


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leTable 3. Risk factors associated to Strongyloides stercoralis infection in HIV patients

Risk

factors Categories df

% Prevalence

(CI 95%)

Odds ratio Heterogeneity Publication bias

OR (95% CI) P-value I²

Cochran Q P-value Egger bias P-value

Sex Male

Female 5

14.43 (5 – 27.44)

10 (3 – 19) 1.93 (1.33-2.81) 0.0005 9.2% 5.51 0.357 -0.96 0.414

Diarrhea Yes

No 13

10.32 (5.89 – 15.82)

5.45 (1.56 – 11.52) 1.78 (1.18-2.69) 0.0052 28% 12.5 0.186 1.03 0.194

CD4+ < 200 cells/µl

> 200 cells/µl 7

8.14 (2.71 – 16.1)

1.41 (0.18 – 3.76) 4.56 (2.44-8.49) <0.0001 0% 5.29 0.624 0.82 0.19


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dr. ehsan ahmadpour (orcid id : 0000-0003-1202-6147) …...strongyloides stercoralis, and affects...

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